Our broad research objectives are to study the mechanisms involved in and factors controlling bone formation, mineralization and resorption. Methods have been developed to characterize quantitatively specific processes related to osteoblastic bone formation, mineralization of matrix, osteocytic functions and osteoclastic bone resorption in histological sections from the diaphysis of the tibia of the rat and from biopsy material from human subjects. These will be combined with biochemical methods to gain fundamental knowledge about the processes of bone formation, mineralization and resorption. Knowledge obtained from this work will be applied to investigate the etiology and treatment of osteoporosis and osteomalacia of human beings. Two such clinical studies, stemming from the concepts and methodology of the proposed more basic work, will be conducted. These are a study of possible toxic causes of metabolic bone diseases and an evaluation of the role of osteocyte metabolism in determining the mechanical properties of bone.